NEUROLOGY & NEUROSURGERY

Harnessing the Glymphatic System to Improve Brain Health

Jan. 14, 2022 - Eden McCleskey

We know sleep is important. We spend one-third of our lives asleep, without which we couldn't function.

But until the 2013 discovery of the glymphatic system by Danish neuroscientist Dr. Maiken Nedergaard, we had no idea why sleep is so important to humans or that the brain uses it to clear its metabolic waste.

Building off this relatively recent discovery, a team of neuroscience researchers and engineers at Houston Methodist, Rice University and Baylor College of Medicine are developing a "sleeping cap" that analyzes the glymphatic system's activity and the flow of cerebrospinal fluid that helps drain the brain of harmful buildup during sleep.

Backed by a U.S. Army $2.8 million grant for the first year of research, the team's goal is to find a way to noninvasively measure, modulate and ultimately stimulate proper cerebrospinal fluid flow in order to treat sleep disorders in real time and stave off neurodegenerative disease.

To make the technology highly accessible — deployed soldiers, for instance, are targeted users — an important secondary goal is to create a prototype that is portable and easy to use.

"It is of great interest to the military to understand the toll of sleep deprivation on its forces and to detect issues and treat them before neurological damage occurs," says Behnaam Aazhang, director of the NeuroEngineering Initiative and J.S. Abercrombie Professor of Electrical and Computer Engineering at Rice. Aazhang's team is responsible for designing and building the cap.

Clearing the cluttered mind

The unique and ambitious scope of the project is underscored by the nascency of the field.

"We used to believe sleep was the time that the body rests, but when you look at the brain during certain sleep cycles, you see it is very, very active," explains Dr. Gavin Britz, director of the Houston Methodist Neurological Institute and the Candy and Tom Knudson Centennial Chair of Neurosurgery. "We also see a very strong link between abnormal sleep and disease states, including heart disease, obesity and neurodegenerative disorders like Alzheimer's. It's clear that something essential happens during sleep."

Thanks to studies by Nedergaard, Britz and other labs in the U.S. and around the world, scientists now have enough data to show that during sleep, the glymphatic system helps the central nervous system clear out its metabolic waste using a network of channels and cerebrospinal fluid, much like the lymphatic system collects and removes unused nutrients and cellular waste from the rest of the body.

Because the brain is highly active, metabolic waste builds up quickly. If the system is interrupted — due to poor sleep quality, lack of sleep or just the slowdown that comes with age — metabolic garbage and byproducts, such as beta-amyloid, the protein associated with Alzheimer's disease, build up between the cells.

"For brain health, sleep is extremely important, and people who don't sleep well have problems clearing toxins from their brains, resulting in a variety of dysfunctions that can affect people in both the short-term and long-term," Dr. Britz says.

Indirect path leads to growing partnership

During an unrelated study on patients with subarachnoid hemorrhage, Dr. Britz and his colleagues Dr. Eugene Golanov and Dr. Angelique Regnier-Golanov discovered that they could manipulate spinal fluid flow using certain molecular targets.

This led to a growing interest in understanding how the glymphatic system works and which patient populations might be helped by controlling it.

The Center for Translational Neural Prosthetics and Interfaces, a collaboration between Rice and Houston Methodist launched in March 2021 to develop technology to solve biomedical problems of the brain and spinal cord, gave the team a leg up when it came to applying for the grant from the Army's Military Operational Medicine Research Program.

"We had already started bringing together the top researchers in neuroscience, engineering and related fields to study how to restore and extend the capabilities of the human brain," Dr. Britz says. "This grant took our partnership to the next level, as we all continue to learn more about the highly complex mechanics of cerebrospinal fluid flow."

The clinical research team, headed by Dr. Britz, is in the process of applying for IRB approval and aims to have preliminary data by summer 2022.

"Ultimately, we're looking at sleep disorders and disease states, but it's always good to start with normal controls to see how it works," Dr. Britz says. "We are starting with healthy volunteers and will measure their cerebrospinal flow at various points, day and night, in a completely noninvasive, risk-free way. At a later stage, we plan to start modulating it to see how it affects glymphatic flow."

A sleep work-around?

The goal of the project is to develop technology that can improve the clearance of waste even without improving the amount or quality of a person's sleep.

"Whether it is psychological stress, trauma, sleep apnea, weight- or heart disease-associated concerns or the natural aging process that tends to make us lighter sleepers, the end result is the same — metabolites accumulate and cause problems for the body and the brain," says Dr. Britz. "We are developing this cap to try and bypass the need for eight hours of high-quality sleep so that even people who sleep poorly can get rid of their waste products efficiently."